Cellular microRNA miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by activating innate antiviral immunity

Porcine reproductive and respiratory syndrome (PRRS) has caused large economic losses in the swine industry in recent years. Current PRRS vaccines fail to effectively prevent and control this disease. Consequently, there is a need to develop new antiviral strategies. MicroRNAs play critical roles in intricate host-pathogen interaction networks, but the involvement of miRNAs during PRRS virus (PRRSV) infection is not well understood. In this study, pretreatment with miR-26a induced a significant inhibition of PRRSV replication and remission of the cytopathic effect in MARC-145 cells, and this antiviral effect was sustained for at least 120 h. Luciferase reporter analysis showed that the PRRSV genome was not the target of miRNA-26a. Instead, RNA-seq analysis demonstrated that miR-26a significantly up-regulated innate anti-viral responses, including activating the type I interferon (IFN) signaling pathway and promoting the production of IFN-stimulated genes. These findings suggest that delivery of miR-26a may provide a potential strategy for anti-PRRSV therapies.